The present invention relates to novel thienopyrimidine-2,4-dione piperidine derivatives and novel furopyrimidine-2,4-dione piperidine derivatives as described further below. The novel compounds are useful as serotonin antagonists and .alpha.-adrenergic blockers with cardiovascular, gastrointestinal and central nervous system activities.
Hypertension afflicts 10-20% of the adult population and is a major cause of many forms of cardiovascular disease (Kaplan, Arch. Intern. Med. 143, 255 (1983)). One method to reduce blood pressure of a hypertensive patient is by the administration of a peripheral .alpha..sub.1 -adrenergic antagonist such as prazosin ("Prazosin: Pharmacology, Hypertension and Congestive Heart Failure," M. D. Rawlins, Ed., 1981). This type of drug effects peripheral vasodilation which reduces the pressure necessary for circulation. Another method to treat hypertension is by the administration of a selective serotonin (5-HT.sub.2) antagonist such as ketanserin (Proceedings of the 10th Scientific Meeting of the International Society of Hypertension, J. Cardiovascular Pharmacol. 7, Suppl. 7 (1985)). The role of serotonin (5-HT.sub.2) in the vascular system has been reviewed in detail (Houston et al., Drugs 31, 149 (1986)). Drugs of this type have also been shown to inhibit platelet aggregation, tracheal smooth muscle contraction and gastrointestinal smooth muscle contraction, and to treat CNS disorders such as anxiety (Janssen, Trends in Pharmacological Sciences 4, 198 (1983); Janssen, J. Cardiovascular Pharmacol. 7, Suppl. 7 (1985)). They are therefore useful as cardioprotective agents, antianginals, afterload reducing agents in congestive heart failure and in the treatment of various peripheral vascular disorders.
Press et al., U.S. Pat. No. 4,670,560, discloses the use of thienopyrimidine-2,4-dione derivatives as antihypertensive or general vasodilating agents. All of the compounds claimed by Press et al. are aryl piperazine derivatives of the general formula ##STR1## U.S. patent application Ser. No. 856,561, filed on Apr. 28, 1986, which issued as U.S. Pat. No. 4,703,120 on Oct. 27, 1987, claims furo[3,4-d]pyrimidine-2,4-dione derivatives which are useful as antihypertensive or general vasodilating agents. All of the compounds claimed in that application are aryl piperazine derivatives of the general formula